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Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration.

ABSTRACT: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents.A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups.With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome-positive, and Philadelphia chromosome-like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL.The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL.

SUBMITTER: Pui CH

PROVIDER: S-EPMC4567699 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration.

Pui Ching-Hon CH Yang Jun J JJ Hunger Stephen P SP Pieters Rob R Schrappe Martin M Biondi Andrea A Vora Ajay A Baruchel André A Silverman Lewis B LB Schmiegelow Kjeld K Escherich Gabriele G Horibe Keizo K Benoit Yves C M YC Izraeli Shai S Yeoh Allen Eng Juh AE Liang Der-Cherng DC Downing James R JR Evans William E WE Relling Mary V MV Mullighan Charles G CG

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20150824 27

<h4>Purpose</h4>To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents.<h4>Methods</h4>A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups.<h4>Results</h4>With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide a ...[more]

PMID: 26304874

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Project description:Comprehensive studies on neutropenia and infection-related complications in patients with acute lymphoblastic leukemia (ALL) are lacking.We evaluated infection-related complications that were grade??3 on National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0) and their risk factors in 409 children with newly diagnosed ALL throughout the treatment period.Of the 2420 infection episodes, febrile neutropenia and clinically or microbiologically documented infection were seen in 1107 and 1313 episodes, respectively. Among documented infection episodes, upper respiratory tract was the most common site (n?=?389), followed by ear (n?=?151), bloodstream (n?=?147), and gastrointestinal tract (n?=?145) infections. These episodes were more common during intensified therapy phases such as remission induction and reinduction, but respiratory and ear infections, presumably viral in origin, also occurred during continuation phases. The 3-year cumulative incidence of infection-related death was low (1.0±0.9%, n?=?4), including 2 from Bacillus cereus bacteremia. There was no fungal infection-related mortality. Age 1-9.9 years at diagnosis was associated with febrile neutropenia (P?=?0.002) during induction and febrile neutropenia and documented infection (both P?<?0.001) during later continuation. White race was associated with documented infection (P?=?0.034) during induction. Compared with low-risk patients, standard- and high-risk patients received more intensive therapy during early continuation and had higher incidences of febrile neutropenia (P?<?0.001) and documented infections (P?=?0.043). Furthermore, poor neutrophil surge after dexamethasone pulses during continuation, which can reflect the poor bone marrow reserve, was associated with infections (P?<?0.001).The incidence of infection-related death was low. However, young age, white race, intensive chemotherapy, and lack of neutrophil surge after dexamethasone treatment were associated with infection-related complications. Close monitoring for prompt administration of antibiotics and modification of chemotherapy should be considered in these patients.

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Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration.

Publications

Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration.

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